We have identified three distinct regulatory circuits involved in the modulation of in vitro antibody responses. Each circuit has a defined inducer cell, a defined transducer cell, a defined effector cell and a defined target(s). The first circuit to be activated is the feedback suppression circuit, which activates suppressor effector T cells that, in turn, suppress both helper and inducer of suppression activities. The second circuit, activated under more vigorous immunization conditions, is the contrasuppressor circuit, which renders the target cells of suppression resistant to suppressor effects. This circuit is critical in hyperimmunization and probably in autoimmunity as well. It appears to recognize antigen complexed to Ig, which would make sense in terms of its proposed functions. The third circuit, identical to that described as a suppressor circuit by Tada and colleagues has, as its major target, the prevention of contrasuppressor activation. Cells in each of these circuits have been delineated by cell surface antigens and, in some instances, molecular products of these cells have been isolated that mimic the activity of the cell producing them. In the coming year, these studies will be extended as follows: Clones or T-cell hybrids expressing the various functions will be produced and characterized. Monoclonal antibodies to each of the subsets will be produced and characterized in the expectation that they will be of use in isolating the molecular products. Antibodies to the molecular products will be prepared by immunization of mice and rats with the isolated molecules leading to preparation of monoclonal antibodies. Finally, the molecules will be characterized in terms of molecular weight, isoelectric point and immunochemically, in preparation for screening cDNA libraries prepared from clones or hybrids for mRNA encoding each of these regulatory molecules.